Previous investigations focusing on the relationship diabetes mellitus and bone homeostasis have been directed mostly towards the detection of hormonal deficiencies or towards insulin therapy. Our goal in this proposed study is to determine the effects of diabetes on the relative amounts, structures and functions of bone matrix proteins. Ultimately, we hope to relate changes of structure and/or quantities in these proteins with their possible roles in bone mineralization. Toward this end we plant experiments with the long bones of control and streptozo-tocin-induced diabetic rats in order to detect differences in: (a) The amount of total protein. (b) The individual amounts of collagen, Bone Gla Protein (BGP or also called Osteocalcin) and the major phosphoproteins. Evidence to date indicate that all these proteins are involved in the process or regulation of bone mineralization. (c) The rate and extent of nonenzymatic glycosylation of the above bone matrix proteins. Nonenzymatic glycosylation is a postranslational reaction in which glucose becomes covalently attached to free amino groups of proteins. The reaction is concentration-dependent on glucose, and the rate of reaction has been found to increase in serum and other vascularized proteins in the hyperglycemic (diabetic) state. Since bone is well-vascularized, the bone matrix proteins should also be glycosylated in a like manner. (d) The function of native and glycosylated proteins. Glycosylation of bone proteins might cause protein conformational changes, and in all likelihood, functional changes. (e) The extent and functional changes caused by postranslational modifications, (e.g., hydroxylation of proline and lysine, carbohydrate attachment, phosphorylation) of the above proteins.